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Biomedical subjects

B Mackay

Publications and source records attributed to B Mackay.

At least 19 recordsLinked to original sources
PubMed2000

Molecular changes in the bronchial epithelium of patients with small cell lung cancer.

To better understand the pathways involved in the pathogenesis of small cell lung carcinoma (SCLC), we compared the patterns of molecular changes present in these tumors and their accompanying bronchial epithelium with those present in the other two major types of lung cancer [squamous cell carcinoma (SQC) and adenocarcinoma (ADC)]. We obtained DNA from 68 microdissected invasive lung tumors (22 SCLCs, 21 ADCs, and, 25 SQCs) and 119 noncontiguous foci of histologically normal or hyperplastic epithelia from 10 tumors of each histological type. We determined loss of heterozygosity and microsatellite alterations at 12 chromosomal regions frequently deleted in lung cancers using 19 polymorphic microsatellite markers. Our major findings are as follows: (a) the mean index of allelic loss in SCLC (0.85) and SQC (0.71) tumors was higher than that in ADC (0.39) tumors; (b) although there was considerable overlap, each tumor type had a characteristic pattern of allelic loss; (c) most samples of bronchial epithelium accompanying SCLC (90%) had allelic loss at one or more loci compared with samples accompanying SQC (54%) or ADC (10%); (d) the mean index of allelic loss was much higher in bronchial epithelial samples from SCLC (0.27) than in those from SQC (0.08) or ADC (0.01); and (e) although the mean indices of microsatellite alterations in the tumor types were similar, the bronchial epithelial samples accompanying SCLC had a 10-fold higher mean index (0.063) than those accompanying SQC (0.006) or ADC (0.006). Our findings indicate that extensive genetic damage in the accompanying normal and hyperplastic bronchial epithelium is characteristic of SCLC tumors and suggest major differences in the pathogenesis of the three major lung cancer types.

Adenocarcinoma↗
PubMed1999

Allelic losses at chromosome 8p21-23 are early and frequent events in the pathogenesis of lung cancer.

Allelic losses on the short arm of chromosome 8 (8p) have been reported as frequent events in several cancers, including lung. However, no comprehensive mapping analysis of chromosome 8p in lung cancer tumors has been performed, and no data are available about the stage at which these abnormalities occur during the multistage development of lung cancer. Using 26 microsatellite markers, we mapped the chromosome 8 regions frequently deleted in lung cancer in 13 small cell carcinoma and 17 non-small cell lung carcinoma cell lines and in 68 microdissected archival primary lung tumors (22 small cell lung carcinomas, 25 squamous cell carcinomas, and 21 adenocarcinomas). We also studied the role of 8p deletions in lung cancer pathogenesis by examining 95 microdissected normal epithelium and preneoplastic samples from 11 surgically resected squamous cell lung carcinomas and from 58 bronchoscopy biopsy samples obtained from 31 current and former smokers. High frequencies of deletions at 8p21-23 regions were detected in lung cancer cell lines and in primary lung tumors. Deletions commenced early during the multistage development of lung cancer at the hyperplasia/metaplasia stage in cancer patients and in smokers without cancer. Allelic deletions persisted for up to 48 years after smoking cessation. There was a progressive increase of the overall 8p21-23 loss of heterozygosity frequency and in the size of the deleted region with increasing severity of histopathological preneoplastic changes. In epithelial samples from resected squamous cell lung carcinomas, we compared the presence of loss of heterozygosity at 8p21-23 with deletions at chromosomes 3p and 9p. Of interest, the pattern of deletions was not random, and 8p21-23 allelic losses always followed 3p deletions and usually followed 9p deletions. We conclude that 8p21-23 deletions are frequent and early events in the pathogenesis of lung carcinomas.

Adult↗
PubMed1999

Alveolar adenoma: a histochemical, immunohistochemical, and ultrastructural analysis of 17 cases.

Alveolar adenoma of lung is a rare benign neoplasm of uncertain histogenesis. Its rarity hampers characterization of its epithelial and mesenchymal elements. Clinical and histopathologic features of 17 alveolar adenomas were reviewed. Histochemistry was performed on 10 cases, ultrastructural analysis on two, and immunohistochemistry on six cases for pneumocyte markers, thyroid transcription factor (TTF-1), surfactant protein markers pro-SP-B and pro-SP-C, and the Clara cell marker, CC10. Immunohistochemistry was performed in nine cases for desmin, smooth muscle actin, muscle-specific actin, cytokeratin, proliferating cell nuclear antigen (PCNA), factor VIII, and carcinoembryonic antigen. The mean age was 53 years. Seven cases occurred in men, and nine occurred in women. The age and sex were not known for one patient. The tumors were coin lesions on chest radiographs in asymptomatic patients except for one (cough). The mean size was 2.2 cm. The tumors were well demarcated with multiple cystic spaces containing granular material. Mostly type 2 pneumocytes lined the cystic spaces with fewer type 1 cells and no Clara cells. This was confirmed by staining for TTF-1, pro-SP-B, and pro-SP-C and by ultrastructure. CC10 was negative in all cases. The stroma varied from prominent spindle cells with a myxoid matrix to thin alveolar septa. The interstitial spindle cells resembled fibroblasts by immunohistochemistry and ultrastructure. Follow-up data available in five cases showed no recurrence at 2, 2, 5, 8, and 13 years. In summary, alveolar adenoma is a benign neoplasm consisting of an intimate admixture of alveolar epithelial and septal mesenchymal tissue. Most of the epithelial cells are type 2 pneumocytes, and the interstitial stromal cells are fibroblasts or fibroblast-like cells. Recognition of its characteristic morphological appearance allows for its distinction from other benign lesions of the lung.

Adenoma↗
PubMed1999

Clear cell sarcoma of kidney in an adolescent and in young adults: a report of four cases with ultrastructural, immunohistochemical, and DNA flow cytometric analysis.

Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29-202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.

Adolescent↗
PubMed1999

Effect of various ions, pH, and osmotic pressure on oxidation of elemental sulfur by Thiobacillus thiooxidans.

The oxidation of elemental sulfur by Thiobacillus thiooxidans was studied at pH 2.3, 4.5, and 7.0 in the presence of different concentrations of various anions (sulfate, phosphate, chloride, nitrate, and fluoride) and cations (potassium, sodium, lithium, rubidium, and cesium). The results agree with the expected response of this acidophilic bacterium to charge neutralization of colloids by ions, pH-dependent membrane permeability of ions, and osmotic pressure.

Acidithiobacillus thiooxidans↗
PubMed1999

Phase II trial of liposome-encapsulated doxorubicin, cyclophosphamide, and fluorouracil as first-line therapy in patients with metastatic breast cancer.

PURPOSE: To determine the efficacy and safety profile, including the risk for cardiac toxicity, of liposome-encapsulated doxorubicin (TLC D-99), fluorouracil (5-FU), and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one women were registered in this phase II study. All patients had measurable disease and no previous chemotherapy for MBC. Treatment consisted of TLC D-99 60 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and 5-FU 500 mg/m2 on days 1 and 8 every 3 weeks. Serial cardiac monitoring, including endomyocardial biopsies, was performed. RESULTS: The overall response rate was 73% (95% confidence interval, 57% to 86%). The median duration of response was 11.2 months, the median time to treatment failure was 8.1 months, and the median overall survival duration was 19.4 months. The median number of cycles per patient was 10. The median cumulative dose of TLC D-99 was 528 mg/m2. Ten patients required hospitalization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectively. Twenty-one patients reached a cumulative doxorubicin dose greater than 500 mg/m2. Three patients (7%) were withdrawn from the study due to protocol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to < or = 40%, and one because her endomyocardial biopsy result was grade 1.5. One patient had congestive heart failure that was probably nonanthracycline related. CONCLUSION: This chemotherapy regimen, including TLC D-99, was highly active against MBC and associated with low cardiac toxicity despite high cumulative doses of doxorubicin.

Adult↗
PubMed1999

Deletions of chromosome 4 at multiple sites are frequent in malignant mesothelioma and small cell lung carcinoma.

Recent allelotyping studies suggest that allelic losses at one or both arms of chromosome 4 are frequent in several tumor types. Cytogenetic studies of malignant mesothelioma (MM) and comparative genomic hybridization analyses of small cell lung carcinoma (SCLC) suggest that chromosome 4 deletions may also play a role in these tumor types, although these results have not been confirmed by allelotyping. In an effort to more precisely identify and map the locations of putative tumor suppressor gene(s) on chromosome 4 involved in the pathogenesis of these tumors, we performed loss of heterozygosity studies using 16 polymorphic microsatellite markers. After precise microdissection of archival surgical cases, we studied DNA obtained from 20 MMs, 21 SCLCs, and 20 non-SCLCs (NSCLCs). In addition, DNA from 14 SCLC and 17 NSCLC cell lines and corresponding B lymphoblastoid lines were studied. In MM and SCLC, we observed frequent losses at three nonoverlapping regions: (a) 4q33-34 (region R1; >80%); (b) 4q25-26 (region R2; >60%); and (c) 4p15.1-15.3 (region R3; >50%). Losses at these sites occurred at lower frequencies in NSCLC (>20-30%). Data from tumors and cell lines were similar. In MM and SCLC, the most frequently observed pattern was loss at all three regions. However, in NSCLC, the most frequent pattern was loss at R3 alone. Our study has delineated three nonoverlapping regions of frequent deletions on chromosome 4 in MM and SCLC, suggesting that there may be three putative suppressor genes on chromosome 4, the inactivation of which may be important in the pathogenesis of these tumor types.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Electron microscopy in tumor diagnosis: indications for its use in the immunohistochemical era.

The electron microscope reveals much more information on tumor cell structure than can be obtained with the light microscope, and some of the data are useful in diagnostic studies. In this review, major contributions of electron microscopy in the main tumor categories are discussed. To select between immunocytochemistry and electron microscopy, the probable contributions of each in the context of the particular case must be assessed. Usually, electron microscopy will only be requested after a battery of immunostaining procedures has been performed and found to be insufficient, but there are occasions when ulstrastructural study is logically the first choice after routine light microscopy. It is worth taking tissue for possible electron microscopy from any tumor that is known or anticipated to be a diagnostic problem.

Biomarkers, Tumor↗
PubMed1997

Neuroendocrine tumors of the lung. Pathology and molecular biology.

Our understanding of the molecular genetic changes in lung cancer pathogenesis is advancing rapidly with several specific genes and chromosomal regions having been identified. As the biochemical functions of the proteins encoded by these genes are discovered, they appear to fall into several growth regulatory pathways. The large number of genetic lesions in clinically evident lung cancer has prompted searching for mutations in preneoplastic lung tissue before the pathologic evidence of cancer as a tool for early molecular diagnosis. In addition, these markers need to be rigorously assessed for their prognostic importance. Finally, understanding the molecular basis of lung cancer should allow "translation" of these findings from the bench to the bedside. These include very early molecular diagnosis, identification of persons at highest risk of developing lung cancer to allow for more effective smoking cessation strategies, chemoprevention, and very early treatment studies (clinical studies beginning); rational development of novel therapies such as immunization against tumor-specific mutant peptides (clinical studies ongoing); blocking the expression of activated oncogenes (such as with antisense or triple helix agents); and replacing defective tumor suppressor genes (clinical studies ongoing).

Carcinoid Tumor↗
PubMed1996

Ewing's sarcoma and peripheral primitive neuroectodermal tumor: an interim report.

The primitive neuroectoderm and its progeny seemingly give rise to an ever-increasing number of clinicopathologic entities. Ewing's sarcoma and peripheral primitive neuroectodermal tumor have recently been united by relatively unique antigens expressed by the MIC-2 gene, commonly coexpressed neural markers, and cytogenetic and molecular genetic abnormalities. Because of these factors, the current thinking is that Ewing's sarcoma and the peripheral primitive neuroectodermal tumor are parts of a phenotypic spectrum. We present an "interim report" on this group of neoplasms, emphasizing their presentation in the head and neck.

Female↗
PubMed1995

Predictors of early deterioration and mortality in black Americans with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Black Americans with spontaneous intracerebral hemorrhage (SICH) may have unique clinical characteristics that affect outcome. The aim of this study was to determine the prognostic value of clinical characteristics and initial CT scan for outcome in black Americans with SICH. METHODS: Clinical and demographic data were extracted from the charts of 182 consecutive black Americans admitted for SICH diagnosed by clinical criteria and initial CT scan. Hemorrhage volumes were calculated from admission CT scans by a computerized method. Univariate and multiple logistic regression analyses were performed to determine independent predictors of early deterioration (defined as a decrease from an initial Glasgow Coma Scale score > 12 by > or = 4 points within 24 hours from presentation) and mortality. RESULTS: Both hemorrhage volume and ventricular extension were significant, independent predictors of early deterioration (odds ratio [OR], 6.78; 95% confidence interval [CI], 1.89 to 24.35 and OR, 4.67; 95% CI, 1.30 to 16.72, respectively) and mortality (OR, 6.66; 95% CI, 2.85 to 15.58 and OR, 4.23; 95% CI, 1.82 to 9.82, respectively). A Glasgow Coma Scale score < or = 12 also predicted mortality (OR, 3.23; 95% CI, 1.46 to 7.14). Initial mean arterial pressure was not an independent predictor of early deterioration or mortality. CONCLUSIONS: Hemorrhage volume and ventricular extension are the best predictors of early deterioration and mortality in black Americans with SICH.

Black People↗
PubMed1995

Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial.

BACKGROUND AND PURPOSE: CGS 19755 is a competitive N-methyl-D-aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke. METHODS: At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee-evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg. RESULTS: Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of > or = 70 at the terminal visit. CONCLUSIONS: We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.

Acute Disease↗
PubMed1995

Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia.

PURPOSE: To estimate the incidence of idarubicin (IDA)-related cardiomyopathy in acute myeloid leukemia (AML) and myelodysplasia (MDS). PATIENTS AND METHODS: We analyzed a group of 127 AML/MDS patients who received IDA-based induction and postremission or salvage therapy and achieved a complete remission (CR) that lasted > or = 12 weeks for the development of IDA-related congestive heart failure (CHF). CHF was defined as definite if a resting left ventricular ejection fraction (LVEF) of < or = 45% measured by radionuclide ventriculogram (RV) accompanied the clinical diagnosis of CHF, which had to be made during or within 6 months of receiving IDA and for which no other cause was apparent; without RV confirmation, the diagnosis was considered probable. Patients who had RVs performed were evaluated for decreasing LVEF. Older age (> or = 70 years), prior/sequential anthracycline/mitoxantrone (anthraquinone) therapy, and cardiac disease/hypertension were evaluated as risk factors for the development of CHF. RESULTS: One hundred fifteen patients were assessable (median age, 40 years; median dose, 96 mg/m2). Sixty-five had RVs performed during therapy; 43 had risk factors. The probability of IDA-related cardiomyopathy was 5% at a cumulative IDA dose of 150 to 290 mg/m2, with 18 patients receiving doses greater than 150 mg/m2. At a cumulative IDA dose of 150 mg/m2, the probability of a mild or greater asymptomatic decrease probability of a mild or greater asymptomatic decrease in LVEF (> or = 10% to a level < or = 50%) was 18%, whereas the probability of a moderate or greater asymptomatic decrease in LVEF (> or = 15% to a level < or = 45%) was 7%. No patient with asymptomatic LVEF decreases developed CHF. CHF was more frequent in patients with prior/sequential exposure to anthracyclines/mitoxantrone (P = .01). CONCLUSION: In this patient group, IDA-related cardiomyopathy was uncommon with cumulative IDA doses of up to 290 mg/m2. Asymptomatic LVEF decreases were more frequent, but their predictive value for the development of CHF is unclear.

Adolescent↗
PubMed1995

Nodular spindle-cell vascular transformation of lymph nodes. A benign process occurring predominantly in retroperitoneal lymph nodes draining carcinomas that can simulate Kaposi's sarcoma or metastatic tumor.

We describe a vasoproliferative nodular spindle-cell lesion representing a variant of vascular transformation of lymph-node sinuses and designated a nodular spindle-cell vascular transformation of lymph nodes. The lesion is most frequently identified in retroperitoneal lymph nodes excised in association with radical nephrectomies for renal cell carcinoma, but it can also be present in association with other malignant tumors. Occasionally it is seen in superficial lymph nodes in patients with no history of malignant neoplasms. This lesion can be confused with Kaposi's sarcoma or with a metastatic sarcomatoid carcinoma because of its spindle-cell composition, cellularity, occasional high mitotic activity, and frequent occurrence in the regional lymphatic drainage of a known malignancy.

Adult↗
PubMed1994

Glomus tumor of the female external genitalia: a report of two cases.

Glomus tumors occurring in the external genitalia of two women aged 53 and 46 years, respectively, are reported. One of the tumors was clitoral and the other arose in the periurethral area of the vulva. The diagnosis in one case was supported by immunocytochemical analysis. Electron microscopy was performed on both tumors. Only two glomus tumors involving the female external genitalia have been reported in the literature. The tumors we describe appeared to be morphologically similar to the glomus tumors that typically arise in the distal extremities.

Female↗
PubMed1994

Granular cell tumors.

The skin and subcutaneous tissue and mucosae of the head and neck are areas of predilection for granular cell tumors. These often histogenetically enigmatic lesions have two principal clinicopathologic presentations: an infantile (congenital) epulis form of the gnathic gingiva and a noncongenital soft tissue and aerodigestive form. Recurrences of either form are largely attributable to marginal excision and, for all sites, approach 15%. A malignant granular cell tumor is recognized, but requires rigorous histologic confirmation.

Age Factors↗
PubMed1993

Intra-abdominal desmoplastic small cell tumor: a light microscopic, immunocytochemical, ultrastructural, and flow cytometric study.

The clinical, microscopic, and immunohistochemical features of 22 intra-abdominal desmoplastic small cell tumors are presented. Ten tumors also were studied by electron microscopy, and flow cytometry was performed in 11 cases. Nineteen patients were male and three were female; their ages ranged from 17 to 38 years (mean, 27 years). With the exception of one case, which arose in the scrotum, all the tumors originated within the abdomen or pelvis and multiple peritoneal nodules were typical. Five tumors also involved the retroperitoneum. The study demonstrates that the range of histology these tumors can display is broader than has been realized previously. The immunohistochemical and ultrastructural findings show evidence for epithelial, mesenchymal, and neuroendocrine phenotypes, raising the possibility that the tumors may be blastomas. Nine tumors were diploid, one tetraploid, and one aneuploid. Sixteen patients died of widespread metastases 8 to 50 months (mean, 25 months) from the time of diagnosis, and five were alive with known evidence of disease. One patient had no evidence of recurrence, but the follow-up of the case was only 10 months.

Abdominal Neoplasms↗